Vascular occlusion by neutrophil extracellular traps in COVID-19.
Aggregated neutrophil extracellular traps
Coagulopathy
Endothelialitis
Immunothrombosis
SARS-CoV-2
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
19
06
2020
revised:
07
07
2020
accepted:
13
07
2020
pubmed:
4
8
2020
medline:
4
9
2020
entrez:
4
8
2020
Statut:
ppublish
Résumé
Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry. Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage. These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage. Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.
Sections du résumé
BACKGROUND
BACKGROUND
Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood.
METHODS
METHODS
Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.
PATIENT FINDINGS
METHODS
Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.
INTERPRETATION
CONCLUSIONS
These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.
FUNDING
BACKGROUND
Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.
Identifiants
pubmed: 32745993
pii: S2352-3964(20)30300-5
doi: 10.1016/j.ebiom.2020.102925
pmc: PMC7397705
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102925Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Martin Herrmann served as adviser to Neutrolis, Cambridge, MA. The remaining authors declare no financial competing interests related to the study.
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